rs75709682

Positions:

• chr4-73419619-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000295897.9(ALB):​c.1765G>A​(p.Glu589Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALB ENST00000295897.9 missense
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 3.69

Genes affected

ALB (HGNC:399): (albumin) This gene encodes the most abundant protein in human blood. This protein functions in the regulation of blood plasma colloid osmotic pressure and acts as a carrier protein for a wide range of endogenous molecules including hormones, fatty acids, and metabolites, as well as exogenous drugs. Additionally, this protein exhibits an esterase-like activity with broad substrate specificity. The encoded preproprotein is proteolytically processed to generate the mature protein. A peptide derived from this protein, EPI-X4, is an endogenous inhibitor of the CXCR4 chemokine receptor. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALB	NM_000477.7	c.1765G>A	p.Glu589Lys	missense_variant	13/15	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1765G>A	p.Glu589Lys	missense_variant	13/15	1	NM_000477.7	ENSP00000295897	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.000224 Hom.: 0

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

ALBUMIN OSAKA 1 Other:1

other, no assertion criteria provided

literature only

OMIM

Jul 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;.;.;.;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.;.;.
MutationTaster	Benign	0.70	N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D;.;.;D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.012	D;.;.;D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D;D
Polyphen		0.22	B;.;.;P;B;.;P
Vest4		0.44
MutPred		0.49		Gain of ubiquitination at E589 (P = 0.0211);.;.;.;.;Gain of ubiquitination at E589 (P = 0.0211);.;
MVP		0.83
MPC		0.37
ClinPred		0.76	D
GERP RS		6.1
Varity_R		0.50
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75709682; hg19: chr4-74285336;